Oral levosimendan in patients with severe chronic heart failure --the PERSIST study.
BACKGROUND
Intravenous levosimendan improves symptoms in acutely decompensated heart failure.


OBJECTIVE
To evaluate the effects of oral levosimendan in severe chronic heart failure (CHF).


METHODS
307 patients with NYHA IIIB-IV CHF were randomly assigned, double-blind, to levosimendan 1 mg once or twice daily or placebo for at least 180 days. An exploratory primary end-point, the Patient Journey, a composite consisting of repeated symptom assessments, worsening heart failure and mortality during 60 days was used. Minnesota Living with Heart Failure quality of life score (MLHFQoL) and NT-proBNP were assessed repeatedly.


RESULTS
Patients assigned to a lower dose of levosimendan had more severe CHF at baseline. No differences in symptoms emerged and worsening heart failure events and death were similar resulting in a similar Patient Journey score with levosimendan and placebo (p=0.567). Compared to placebo, a net improvement of 3-4 points in MLHFQoL at several time-points in favour of the combined levosimendan groups was observed (p<0.001) which was accompanied by a substantial and persistent reduction in NT-proBNP (-30-40%) (p<0.001).


CONCLUSIONS
Levosimendan improved QoL and decreased NT-proBNP but did not improve the Patient Journey composite in patients with severe CHF. Further research with this compound is warranted to clarify safety and efficacy.
Nieminen
Markku S
MS
Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. markku.nieminen@hus.fi
Cleland
John G F
JG
Eha
Jaan
J
Belenkov
Yuri
Y
Kivikko
Matti
M
Põder
Pentti
P
Sarapohja
Toni
T
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D011594:Psychometrics; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D012720:Severity of Illness Index; D000077464:Simendan; D011795:Surveys and Questionnaires
D015415:Biomarkers; D002316:Cardiotonic Agents; D006835:Hydrazones; D010446:Peptide Fragments; D011724:Pyridazines; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000077464:Simendan